The present invention generally provides devices, systems, methods, and kits for labeling and/or tracking inventories of elements. In a particular embodiment, the invention provides improved identification systems and methods which make use of labels that emit differentiable spectra, the spectra preferably including a number of signals having measurable wavelength maxima, minima, and/or intensities.
Tracking the locations and/or identities of a large number of items can be challenging in many settings. Barcode technology in general, and the Universal Product Code in particular, has provided huge benefits for tracking a variety of objects. Barcode technologies often use a linear array of elements printed either directly on an object or on labels which may be affixed to the object. These barcode elements often comprise bars and spaces, with the bars having varying widths to represent strings of binary ones, and the spaces between the bars having varying widths to represent strings of binary zeros.
Barcodes can be detected optically using devices such as scanning laser beams or handheld wands. Similar barcode schemes can be implemented in magnetic media. The scanning systems often electro-optically decode the label to determine multiple alphanumerical characters that are intended to be descriptive of (or otherwise identify) the article or its character. These barcodes are often presented in digital form as an input to a data processing system, for example, for use in point-of-sale processing, inventory control, and the like.
Barcode techniques such as the Universal Product Code have gained wide acceptance, and a variety of higher density alternatives have been proposed. Unfortunately, these known barcodes are often unsuitable for labeling many xe2x80x9clibrariesxe2x80x9d or groupings of elements. For example, small items such as jewelry or minute electrical components may lack sufficient surface area for convenient attachment of the barcode. Similarly, emerging technologies such as combinatorial chemistry, genomics and proteomics research, microfluidics, micromachines, and other nanoscale technologies do not appear well-suited for supporting known, relatively large-scale barcode labels. In these and other ongoing work, it is often desirable to make use of large numbers of fluids, and identifying and tracking the movements of such fluids using existing barcodes is particularly problematic. While a few chemical encoding systems for chemicals and fluids had been proposed, reliable and accurate labeling of large numbers of small and/or fluid elements remained a challenge.
Small scale and fluid labeling capabilities have recently advanced radically with the suggested application of semiconductor nanocrystals (also known as Quantum Dot particles), as detailed in U.S. patent application Ser. No. 09/397,432, the full disclosure of which is incorporated herein by reference. Semiconductor nanocrystals are microscopic particles having size-dependent electromagnetic signal generation properties. As the band gap energy of such semiconductor nanocrystals vary with a size, coating and/or material of the crystal, populations of these crystals can be produced having a variety of spectral emission characteristics. Furthermore, the intensity of the emission of a particular wavelength can be varied, thereby enabling the use of binary or higher order encoding schemes. A label generated by combining semiconductor nanocrystals having differing emission signals can be identified from the characteristics of the spectrum emitted by the label when the semiconductor nanocrystals are energized.
While semiconductor nanocrystal-based inventory control schemes represent a significant advancement for tracking and identifying many elements of interest, still further improvements would be desirable. In general, it would be desirable to provide improved identification systems, methods for identifying elements, and/or identifiable groups or libraries of elements. It would be particularly beneficial if these improved inventory and identification systems enhanced the accuracy, reliability and robustness of the identifications provided by the system. Ideally, these improvements should allow enhanced differentiation of the labeled elements without significantly increasing the overall costs, complexity and/or size of the labels and associated system components. At least some of these objectives may be provided by the inventions described hereinbelow.
The present invention generally provides improved devices, systems, methods, kits, and compositions of matter for identification of elements of interest. The techniques of the present invention will often be adapted for use in tracking and/or identifying a large number or library of elements. These tracking or identification techniques are particularly well suited for use with fluids (such as liquids, solutions, gases, chemicals, biological fluids, and the like) and small items (such as jewelry, cells, components for assembly, and the like), but may also be used with a wide range of identifiable elements (including consumer products, powders, biological organisms, compositions of matter, and the like.) The inventory control techniques of the present invention will often make use of signals generated by one or more semiconductor nanocrystals. Semiconductor nanocrystals can be fabricated to absorb and/or emit signals at discrete wavelengths and intensities. The discrete signals from semiconductor nanocrystals can be combined to form a large number of differentiable spectral codes. More specifically, semiconductor nanocrystals can have absorption and emission characteristics that vary with their size and composition. By fabricating populations of semiconductor nanocrystals to generate signals at discrete wavelengths, the differing populations of semiconductor nanocrystals can be selectively combined to define labels having differentiable spectral codes.
While semiconductor nanocrystals are particularly advantageous for defining complex spectral codes, the labels may also comprise any of a wide variety of alternative signal-emitting or other markers, including organic or inorganic fluorescent dyes, Raman scattering materials, and the like. Regardless, the invention enhances the robustness of the spectral codes by a variety of techniques, including the addition of calibrating signals within the label spectra as an aid for code interpretation. This calibration signal can compensate for overall signal variability in wavelength and/or in intensity. Surprisingly, the invention also enhances the number of differentiable codes by limiting the label spectra to a series of signals having discrete wavelengths within separated wavelength ranges or windows, thereby facilitating identification of substantially isolated peak wavelengths from among tightly spaced discrete allowable wavelength increments. The invention also provides methods for establishing an inventory of acceptable labels by either physically testing candidate spectral labels, or by modeling the characteristics of the spectral labels and/or label interpreting system to help insure that the system can accurately differentiate between the different elements of the inventory based on the spectra of the labels.
In a first aspect, the invention provides an identification system. The identification system comprises a plurality of identifiable elements and a plurality of labels. Each label is associated with an identifiable element, and the labels include reference markers and other markers, the labels generating spectra in response to excitation energy. An analyzer identifies the elements from the spectra of the associated labels by calibrating the spectra using reference signals generated by the reference markers.
In many embodiments, the labels comprise semiconductor nanocrystals, with the reference markers often including at least one reference semiconductor nanocrystal. The reference markers may include a plurality of reference semiconductor nanocrystals, the reference markers of each label generating a reference wavelength with a reference intensity. Similarly, the other markers may comprise other semiconductor nanocrystals generating associated signals at associated wavelengths and with associated intensities. The spectra may define an identifiable spectral code, with the other markers optionally comprising code signal markers, the spectra comprising a combination of the reference signals from the reference markers in combination with code signals from the code signal markers
Optionally, the analyzer can, for each label, discretely quantify the other signals of the label by comparison of the other signals with the reference signal. For example, where the reference signal has a reference intensity and the other signals of the label have other intensities, the analyzer can discretely quantify the other intensities by comparison to the reference intensity of that label. This is particularly beneficial when interpreting spectral codes which employ variations in both wavelength and intensity. The intensities may define discrete intensity ratios relative to the associated reference intensities. For example, the other intensities may be integer multiples of the reference intensity, or a variety of regular intensity ratio increments may be provided, with each signal from the other markers having an intensity selected from xc2xd, 1, 1.5, . . . or 3.5 times the intensity of the reference signal. In some embodiments, the signals from the other markers may have an arbitrary, and typically known, intensity relative to the intensity of the reference signal.
To facilitate identification of the reference signal, the reference intensity may be a highest or lowest intensity of the label spectra. Alternatively, at least some of the labels may have a common reference signal wavelength. A variety of alternative reference signal identification criteria may be established, such as selecting a shortest or longest wavelength of the spectra of the label as the reference wavelength, and the like. The analyzer may be adapted to identify the reference signal based on a pre-determined criteria.
Advantageously, the spectral identification system of the present invention is particularly well-suited for use with large numbers of identifiable elements. Typically, the identification system will include at least 10 elements, often having at least 100 elements, often having at least 1,000 elements, and in many embodiments, having at least 10,000 identifiable elements. As the invention enhances the robust interpretation of complex spectral codes, large numbers of such codes may be reliably interpreted with the aid of a calibration signal within the spectra. Nonetheless, the invention may find uses with identification systems having fewer numbers of labels.
In many embodiments, the analyzer will comprise a tangible media embodying a machine-readable code comprising a listing of a plurality of distinguishable labels. Often times, the code will also include a listing of the identifiable elements, and can provide a correlation between each label and an associated identifiable element having the label. The identifiable elements may comprise compositions of matter, fluids, articles of manufacture, consumer products, components for an assembly, and a wide variety of alternative items of interest.
In a related method aspect, the invention provides a method for sensing a plurality of identifiable elements. The method comprises labeling each identifiable element with a reference marker and at least one associated other marker. The markers of a first label from a first identifiable element are energized so that the markers generate signals. A spectrum defined by the combined signals is measured from the first identifiable element. The first identifiable element is identified from the measured spectrum by calibrating the spectrum with reference to a reference signal from the reference marker of the first label.
In another related aspect, the invention provides a library of elements. The library comprises a plurality of identifiable elements, each identifiable element having an associated label with a reference marker. The labels generate spectra in response to an excitation energy. Each spectrum includes a wavelength calibration reference signal from the reference marker.
In another aspect, the invention provides a method comprising labeling an identifiable element with a label, and measuring a spectrum generated by the label. The spectrum comprises a plurality of signals. The element is identified by selecting a first wavelength range encompassing a first signal of the spectra, and by determining a wavelength of the first signal within the first range. Typically, the wavelength of the signal will comprise wavelength having a local and/or overall maximum intensity, often referred to as the peak wavelength of the signal.
Often times, the element will be labeled by applying at least one semiconductor nanocrystal to the element. The semiconductor nanocrystals generate at least some of the signals of the spectra in response to excitation energy.
The method will often further comprise selecting a second wavelength range encompassing a second signal of the spectra, and determining a wavelength of the second signal within the second range. Still further additional wavelength ranges may be selected, and wavelengths identified for each additional signal of the spectra within its associated range. Preferably, no more than one signal of the spectra will be disposed within each wavelength range. By limiting the number of signals within a wavelength range, the various signals of the spectra can be sufficiently separated to avoid excessive overlap of adjacent signals. This allows wavelengths of the signals within each associated wavelength range to be readily identified, even when the signals can occupy any of a plurality of relatively tightly spaced discrete wavelength increments. Accurate selection of an appropriate predetermined wavelength for each signal is significantly facilitated by limiting spacing between adjacent signals.
Typically, the wavelengths of the first and second signals will be determined by selecting the wavelengths of the signals from a plurality of discrete wavelengths within the ranges. The discrete wavelengths within each range can be sufficiently close that if two signals were at adjacent discrete wavelengths within the range they would substantially overlap, optionally overlapping sufficiently to make identification of either or both wavelength peaks of the signals difficult and/or impossible.
In many embodiments, the discrete wavelengths within the ranges will be predetermined. These discrete wavelengths may be separated by about 1 nanometer or more, generally being separated by about 5 nanometers or more, optionally being separated by about 15 nanometers or more, and in many embodiments, being separated by about 30 nanometers or more.
Typically, the wavelength ranges will be separated, ideally being sufficiently separated so that a pair of signals at adjacent discrete wavelengths within two different ranges can have their discrete wavelengths identified independently and relatively easily. Typically, the ranges will be separated by at least about 30 nm, often by at least about 50 nm, and each wavelength range will include at least 1, and often at least 5 predetermined discrete wavelengths. To accommodate relatively large numbers of spectral codes, there will often be at least three non-overlapping ranges, with the wavelength ranges optionally being predetermined. In other embodiments, the wavelength ranges may not be separated. In such embodiments, the encoding system may optionally have signals within two adjacent wavelength ranges separated by at least a predetermined wavelength separation, wavelengths within adjacent ranges typically being separated by at least 30 nm, often being separated by at least about 50 nm.
Optionally, the wavelength may be determined by deciding whether a discrete wavelength is present or absent. Such binary methods will often make use of labels having at least one different signal for each different label. Alternatively, a discrete intensity of at least one wavelength may be measured to provide a higher-order code with more information for a given spectral range.
Where differing materials and their associated labels are to be intermingled, the signals of a first label may optionally be encompassed within a first wavelength range, while the signals of a second label are encompassed within another wavelength range. Separation of the first and second wavelength ranges can help avoid confusion between the intermingled markers of the two labels, allowing each identifiable element to be independently identified.
In a related method aspect, the invention provides a method for sensing a plurality of intermingled labels. The method comprises energizing the labels so that the labels generate signals. A first label is identified by measuring a first discrete wavelength from among a plurality of discrete wavelengths within a first wavelength range. A second label is identified by measuring a second discrete wavelength from among a plurality of discrete wavelengths within a second wavelength range, the first and second wavelength ranges being separated.
Separation of differing wavelengths of differing labels into separate wavelength ranges or windows is particularly useful when tracking fluids which are to be combined. For example, when any of a first plurality of fluids is to be added to any of a second plurality of fluids, maintaining the spectral codes of each group of fluids within a dedicated window can significantly facilitate identification of each fluid in the combination. Similarly, labels may be attached at each process step of a multi-step method so as to indicate the specific processes performed.
In yet another aspect, the invention provides an inventory system comprising a plurality of identifiable elements. A plurality of labels have markers, with each label associated with an element. Each marker generates a signal when energized so that each label emits an identifiable spectrum. At least some of the spectra comprise a plurality of signals, with each signal of the spectra having a discrete wavelength selected within a dedicated wavelength range. The ranges are sufficiently separated so that the signals in different ranges are independently identifiable.
In yet another aspect, the invention provides an inventory label method. The method comprises generating a plurality of candidate labels, and selecting a plurality of acceptably distinguishable labels from among the candidate labels. The acceptable labels are selected by determining spectra emitted by the candidate labels when the candidate labels are energized, and by comparing the spectra of the candidate labels.
Candidate labels may be generated by physically combining a plurality of markers, where each marker emits a marker signal at an associated signal wavelength in response to excitation energy. This also allows the spectra of the labels to be measured by directing excitation energy towards the markers. Alternatively, the spectra of the candidate labels may be determined by modeling a combination of a plurality of marker signals. The individual marker signals may be separately measured, or the marker signals may be calculated by modeling emissions from a manufacturable marker. Preferably, the calculated signals may be adjusted for spectra analyzer characteristics and/or variations of measured marker signals. Often times, at least some of the candidate codes will be compared with a library of distinguishable codes to determine if the candidate codes are acceptable, and the acceptable candidate codes can be added to the library.
In yet another aspect, the invention provides a method for identifying a plurality of identifiable elements. The method comprises energizing a plurality of labels so that a first marker of each label generates a first signal with a first wavelength peak. At least some of the labels comprise multiple-signal labels, and each multiple-signal label has a second marker generating a second signal with a second wavelength peak. The first wavelength peaks are measured, and the second wavelength peak of each multiple-signal label can be measured at a predetermined minimum wavelength separation (or more) from the associated first peak. The labels can then be identified in response to the measured peaks. Generally, each predetermined minimum wavelength separation is at least as large as a full width half maximum (FWHM) of one ore both of the peaks separated thereby.